DESCRIPTION (application abstract) Perturbations in the homeostasis of cells by invading organisms, accumulation of pathologic substances, and uncontrolled cell growth provide the underlying basis for most morbid and mortal illness. As such, the challenge of manipulating cellular functions for desired outcomes, such as cancer eradication, controlling viral infection onset as well as stem cell differentiation collectively toward therapeutic gain lies within the complexity of the system of regulatory circuitries that govern cellular pheno-/genotypes. The goal for this center is to investigate and manipulate the complex cell signaling network circuitries in a time-resolved dynamic manner in order to not only enhance our understanding of individual signaling pathways but also provide vital information on their codependence and interactivities for the potential of controlling the cell phenotype. Our unique approach employs a systemic view of controlling networks that has the ability to i) perturb the cellular network circuitry, ii) conduct real time monitoring of the key signaling elements, iii) interpret and analyze the system's response, and iv) use a global system control algorithm to dissect and analyze the cellular network circuitry. This approach precisely addresses the NIH's vision on NDC that "decisions on the biological systems...guided by the principle that the precise control required to manipulate cellular components will depend upon understanding and using engineering principles". Our objective is not only to extend our understandings of local interactions of cellular components but also globally control cellular functions through regulatory circuitries. Unbalanced signaling pathway, triggered by either external or internal factors, is the hallmark of human disease. This is especially true for conditions like cancers, infectious diseases and stem cell related disorders. This center proposes unique techniques to explore the dynamics of the signaling pathways in these three fields and to dynamically control the outcomes of the network for novel therapeutics.